Current Medicinal Chemistry (v.24, #2)

Meet Our Editorial Board Member by Werner Sieghart (111-111).

Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity by Ignacio Esteban Leon, Juan Fernando Cadavid-Vargas, Ana Laura Di Virgilio, Susana Beatriz Etcheverry (112-148).
Cancer is a group of diseases involving abnormal cell growth. The cells grow uncontrollably with the potential to invade and spread to other parts of the body.
This disease is one of the principal death causes in the world, thus becoming a significant topic of scientific research. On the other hand, transition metals play a fundamental role in different living systems. In particular, Metallodrugs represent new and powerful tools for diverse therapeutic applications. To date, various metallodrugs display interesting biological activities for chemotherapy. In this field, cisplatin was the first inorganic compound with high relevance in cancer treatment. This compound was a leader agent in clinical use. Toxicity and resistance problems trigger the development of other platinum drugs with better clinical perspective and also raise the scientific interest for the putative antitumor properties of V, Ru and Cu compounds. Several scientific articles show that complexes of these metals are the new metal-based drugs used in the treatment of several cancers, such us, lung, colon, breast, bladder, etc.
In this review we recapitulate current information and new advances on antitumor in vitro effects of several organic and inorganic compounds derived from copper, ruthenium and vanadium. These metal derived compounds targeting DNA or cell proteins involved in cell signaling pathways related to cancer. The mechanisms of cell death of these metallodrugs have also been comprehensibly reviewed.
The knowledge of these mechanisms of death and the relationship between chemical structure and biological activity may be useful for the design of new metal-based drugs with promising pharmacologic applications as anticancer agents.

Algae Polysaccharides' Chemical Characterization and their Role in the Inflammatory Process by Noelia Florez, Maria Jesus Gonzalez-Munoz, Daniela Ribeiro, Eduarda Fernandes, Herminia Dominguez, Marisa Freitas (149-175).
Polysaccharides are abundant components in marine macroalgae with potential applications in different areas such as pharmaceutical, biomedical, cosmetics and nutrition. The current interest in these compounds is due to their known bioactivities, conferred by their antiallergic, neuroprotective, gastroprotective, cardioprotective, cytotoxic, anticoagulant/antithrombotic, antiviral, antilipidemic, antinociceptive, and immunomodulatory properties, making them promising bioactive products and biomaterials. The inflammatory process is a complex event mediated by the immune system that culminates in the neutralization and elimination of the offending insult protecting the host and restoring tissue homeostasis. This review focuses on the extraction procedures and chemical characterization of polysaccharides from different classes of algae (Phaeophyceae, Rhodophyceae and Chlorophyceae) and on the studies on their inflammatory process modulatory effect.

Lipids at the Cross-road of Autoimmunity in Multiple Sclerosis by Marcella Reale, Silvia Sanchez-Ramon (176-192).
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and neurodegeneration, driven by a Th17/Th1-immune response, which afflicts mainly young women. Although MS causes are not completely known, it is notorious that the disease is characterized by an extended focal degradation of the myelin sheath, with ulterior axonal and neuronal damage. Lipid molecules play a main dual role in MS, both as target molecules of myelin destruction and as mediators of inflammation. Indeed, recent cumulative evidence suggests that abnormalities in the lipidbinding proteins of myelin and sphingolipid content that confer increased immunogenicity may underlie the autoimmune response against the myelin sheath. CNS is after all, the second organ richer in lipid content after adipose tissue. On the other hand, soluble factors called adipokines, secreted by adipose tissue, modulate inflammatory responses and contribute to metabolic dysfunction, which may be important in MS pathophysiology. Disability accumulation in MS patients is slow but persistent, often leading to a decreased mobility and physical activity, resulting in more weakness, fatigue and associated increased risk of the metabolic syndrome (MetS). In turn, MetS may trigger MS in susceptible individuals and is a bad prognostic factor. Here we review what are the facts linking lipids, MetS and MS, what we do not know yet, and what we should do to move this field forward.

Anti-cancer Drug Delivery Using Metal Organic Frameworks (MOFs) by Mihad Ibrahim, Rana Sabouni, Ghaleb A. Husseini (193-214).
Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks, anti-cancer drug delivery systems have been developed recently using nanocarriers including liposomes, micelles, polyelectrolyte capsules and others.
One of the recent class of nanoparticles investigated for chemotherapeutic use are metal organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or clusters and organic ligands. MOFs are used in many applications including gas/vapor separation, gas storage, catalysis, luminescent materials, and biomedical imaging. These structures have additional features that promote their use as drug carriers in the biomedical field. First, they are nontoxic, biodegradable and have the ability to carry high loadings of the anti-neoplastic agent due to their porous nature. Also, they have well-defined crystalline structures that can be characterized by different analytical techniques and their sizes are suitable to control their in vivo drug release.
This paper reviews the methods used to synthesize MOFs and their recent use as antineoplastic drug delivery carriers.

Bioactive Sutures: A Review of Advances in Surgical Suture Functionalisation by Feras Alshomer, Arul Madhavan, Omar Pathan, Wenhui Song (215-223).
Sutures have been at the forefront of surgical medicine throughout time. With recent advances in suture technology, it is possible to incorporate biologically active substances to enhance suture function and capability. Bioactive sutures represent a modality interest in controlled drug and cell delivery to traumatic sites. In this article, a comprehensive literature search of key bibliographic databases focusing on suture material fabrication and advanced modification was performed. The history, manufacturing process and cost-effectiveness of bioactive sutures are presented. Several novel modifications to enhance function in drug and growth factor delivery and cell therapy are also reviewed. Different antimicrobial drugs and anaesthetics have been shown to be effective in reducing inflammation and bacterial infection. Cellular therapy represents a unique modality augmenting the surgical repair of various soft tissue injuries. We propose a definition of bio-active sutures as biomaterials that are engineered to have controlled tissue interaction to optimise wound/defect healing, in addition to their essential function in tissue approximation.